Candidate: Immediate and Long-term Research Goals: Sheral S. Patel is currently a Pediatric Infectious Diseases fellow at Rainbow Babies and Children's Hospital and the Division of Geographic Medicine, Case Western Reserve University. During the past year, she has investigated red blood cell polymorphisms in the Wosera of Papua New Guinea. Her primary area of interest is the influence of red blood cell polymorphisms on susceptibility to malaria infection. The in vitro malaria parasite growth and invasion assays as well as the epidemiologic components of this study are new approaches for the investigator. Mentored training supplemented by coursework is important to her development as an independent clinical investigator. Research Project: Individuals living in the Wosera, a malaria holoendemic area of Papua New Guinea have many unique red blood cell polymorphisms including ovalocytosis. We hypothesize that the frequency of ovalocytosis is high in the Wosera because it protects the individual from severe malaria infection. This proposal will examine the genetic basis of abnormalities in erythrocyte morphology found in residents of the Wosera, and determine their association with susceptibility to malaria infection. The aims of this project are to 1.) investigate whether known polymorphisms in erythrocyte membrane proteins, including band 3, glycophorin C, spectrin, protein 4.1, and ankyrin, are observed in the Wosera, 2.) perform association studies on individuals from the Wosera with high numbers of ovalocytes and polymorphisms identified in the candidate molecules, 3.) evaluate whether ovalocytosis and genetic polymorphisms in the identified candidate genes affect susceptibility to blood-stage infection with P. falciparum, vivax, malariae, or ovate through prospective casecontrol studies in the Wosera, and 4.) examine the in vitro characteristics of infection and growth of P. falciparum using erythrocytes from individuals living in the Wosera with and without ovalocytosis and genotypically discordant in select candidate genes.